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The metabolic pathway of DL-rolipram was studied in two animal species and in man. Metabolites were isolated from rat, rhesus monkey, and from human urine by preparative HPLC and identified by MS and NMR analysis. In total, the structures of 7 degradation products could be elucidated. Rolipram was metabolized by ether cleavage at the methoxy and cyclopentyloxy groups and by hydroxylation in positions 2 or 3 of the cyclopentyloxy ring followed by sulphation. Additionally, but exclusively in man, the 5-position of the pyrrolidone ring was hydroxylated.
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